Human macrophages when activated by a variety of agents produce lymphocyte activating factor (LAF). LAF exists in a 15,000 mw form which when mixed with serum changes to a 60,000 mw form. Both forms of LAF are mitogenic for peanut agglutinin negative (PNA minus) mouse thymocytes. The higher mw form also induces increased Lyt-1 expression by thymocytes and is mitogenic for human T lymphocytes. Only the lower mw replaces macrophages in lectin induced human T cell proliferation and enhances helper T cell dependent immunoglobulin production by human B cells. The mitogenic effects of LAF can be competitively inhibited by allose. Human T lymphocytes can be activated by lectins or antigens to produce a mitogenic factor(s) (LMF). LMF is also mitogenic for mouse PNA minus thymocytes and elutes in the same two regions off Sephadex as LAF. LMF differs from LAF in that: 1) LMF production is inhibited by suppressor T cells, 2) The 15,000 mw LMF is mitogenic for human B cells as well as for cytoxic T lymphocytes and 3) LMF is not inhibitable by allose. Presumably LAr ana LMF amplify immunological reactions by promoting the growth and differentiation of distinct subpopulations of lymphoid target cells.